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Androgen signaling and post-transcriptional downregulation of Bcl-2 in androgen-unresponsive prostate cancer

Prostate Cancer and Prostatic Diseases volume 7, pages 158–164 (2004)Cite this article

Abstract

We previously characterized the LNCaP prostate cancer progression model and showed that despite loss of Bcl-2 protein in the androgen-unresponsive LNCaP-unresponsive (UR) cells, these cells maintained an increased resistance to the induction of apoptosis. Since the loss of Bcl-2 protein coincided with the progression to androgen-unresponsiveness, we sought to determine if Bcl-2 expression was regulated through androgen signaling pathways. LNCaP-responsive (R) and -UR cells grown in charcoal-stripped serum conditions for 3 months differentiated to a neuroendocrine (NE)-like morphology. Under these conditions, LNCaP-UR cells regained Bcl-2 protein expression, and LNCaP-R cells overexpressed Bcl-2. Chronic exposure to casodex resulted in differentiation of both LNCaP-R and -UR cells to the NE-type morphology accompanied by a marked downregulation of Bcl-2 protein, while Bax protein levels were unchanged. Downregulation of Bcl-2 was post-transcriptional since Bcl-2 message levels were unchanged in LNCaP cells treated with casodex. These data suggest that Bcl-2 is post-transcriptionally modulated by androgen signaling pathways in LNCaP cells.

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Acknowledgements

This work was supported by grants from the Pfeiffer (Gustavus and Louise) Foundation, UNMC/Eppley Cancer Center (LB595), and AstraZeneca LP.

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  1. Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA

    C A Rothermund, V K Gopalakrishnan & J K Vishwanatha

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  1. C A Rothermund
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  2. V K Gopalakrishnan
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  3. J K Vishwanatha
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Correspondence to J K Vishwanatha.

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Rothermund, C., Gopalakrishnan, V. & Vishwanatha, J. Androgen signaling and post-transcriptional downregulation of Bcl-2 in androgen-unresponsive prostate cancer. Prostate Cancer Prostatic Dis 7, 158–164 (2004). https://doi.org/10.1038/sj.pcan.4500717

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